Immunity · 2019
Neutrophil Extracellular Traps Initiate Gallstone Formation.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Muñoz Luis E, Boeltz Sebastian, Bilyy Rostyslav, Schauer Christine, Mahajan Aparna, Widulin Navena, Grüneboom Anika, Herrmann Irmgard, Boada Edgyda, Rauh Manfred, Krenn Veit, Biermann Mona H C, Podolska Malgorzata J, Hahn Jonas, Knopf Jasmin, Maueröder Christian, Paryzhak Solomiya, Dumych Tetiana, Zhao Yi, Neurath Markus F, Hoffmann Markus H, Fuchs Tobias A, Leppkes Moritz, Schett Georg, Herrmann Martin
Аннотация
The presence of gallstones (cholelithiasis) is a highly prevalent and severe disease and one of the leading causes of hospital admissions worldwide. Due to its substantial health impact, we investigated the biological mechanisms that lead to the formation and growth of gallstones. We show that gallstone assembly essentially requires neutrophil extracellular traps (NETs). We found consistent evidence for the presence of NETs in human and murine gallstones and describe an immune-mediated process requiring activation of the innate immune system for the formation and growth of gallstones. Targeting NET formation via inhibition of peptidyl arginine deiminase type 4 or abrogation of reactive oxygen species (ROS) production, as well as damping of neutrophils by metoprolol, effectively inhibit gallstone formation in vivo. Our results show that after the physicochemical process of crystal formation, NETs foster their assembly into larger aggregates and finally gallstones. These insights provide a feasible therapeutic concept to prevent cholelithiasis in patients at risk.